Pyrolytic products from tryptophan and glutamic acid are positive in the mammalian spot test.

Pyrolysates of tryptophan (Trp-P-2) and glutamic acid (Glu-P-1) are known mutagens in in vitro short term mutagenicity tests, and have also shown carcinogenic effects in long term animal studies. The present study demonstrates that they also produce mutations in somatic cells. This result demonstrates the ability of the test to detect carcinogenic and mutagenic compounds.

Immunogenicity evaluation of DNA vaccines that target guinea pig cytomegalovirus proteins glycoprotein B and UL83.

Vaccines are needed for control of congenital human cytomegalovirus (HCMV) infection. Although the species-specificity of cytomegaloviruses precludes preclinical evaluation of HCMV vaccines in animal models, the guinea pig cytomegalovirus (GPCMV), which causes disease in utero, is a relevant model for the study of vaccines against congenital infection. We investigated whether DNA vaccines that target two GPCMV proteins, glycoprotein B (gB) and UL83 (pp65), are capable of eliciting immune responses in vivo. After cloning each gene into an expression vector, DNA was delivered by intramuscular inoculation and by pneumatic epidermal delivery. In Swiss-Webster mice, anti-gB titers were significantly higher after epidermal delivery. After epidermal inoculation in guinea pigs, all gB-immunized animals (n = 6) had antibody responses comparable to those induced by natural infection. Viral neutralization titers ranged from 1:64 to greater than 1:128. A GPCMV UL83 DNA vaccine also elicited an antibody response in all immunized guinea pigs (n = 6) after epidermal administration. Immunoprecipitation and Western blot assays confirmed that immune sera were immunoreactive with virion-associated UL83 and gB proteins. We conclude that DNA vaccines against GPCMV structural proteins are immunogenic, and warrant further investigation in the guinea pig model of congenital CMV infection.

A charge-remote allylic cleavage reaction: Mechanistic possibilities.

The collision-induced allylic cleavage reactions of deuterium-labeled [M - H + 2Li)(+) and [M - H](-) ions of monounsaturated fatty acids were investigated. Three concerted mechanistic possibilities were considered for this process: a l,4-elimination of a vinylic H, a retro-ene reaction, and a l,4-conjugate elimination. A fourth mechanistic possibility, a two-step radical version of the retro-ene and l,4-conjugate elimination reactions, was also considered. The radical reactions are in accord with the isotopic labeling results and offer certain mechanistic consistencies for cleavage of both C-C allyl bonds; they are expected, however, to have large activation energies. The lower-energy concerted alternatives, the retro-ene reaction for cleavage of the proximal and the l,4-conjugate elimination for cleavage of the distal C-C allyl bond, are also consistent with experimental results. The alternative of two different concerted mechanisms for cleavage of the two allyl bonds, however, is at odds with the charge-remote concept.

Mutagenic activity at different stages of an industrial ammonia caramel process detected in Salmonella typhimurium TA100 following pre-incubation.

Mutagenic activity of a commercial ammonia caramel colouring was demonstrated in Salmonella typhimurium TA100 without metabolic activation. The activity in strain TA100 was increased using a 10-min pre-incubation, and a clear dose-response relationship was seen using this method. Investigation of samples taken from the different stages in the industrial process showed a constant level of mutagenic activity in samples from the middle to the end of the heating process with a steep increase in the sample taken after the end of heating. No mutagenic activity was seen in assays with S. typhimurium strains TA1535 and TA98.

FAB MS/MS for phosphatidylinositol, -glycerol, -ethanolamine and other complex phospholipids.

Fast atom bombardment (FAB) of phosphatidylinositol, phosphatidylethanolamine, cardiolipin, phosphatidic acid and phosphatidylglycerol produces a limited number of very informative negative ions. Especially significant is the formation of (M-H)-ions and ions that correspond to the carboxylate portions of these molecules. FAB desorption in combination with collisional activation allows for characterization of fragmentation and determination of structural features. Collisional activation of the carboxylate anion from complex lipids is especially informative. Structural characterization of the fatty acids can be achieved as the released saturated carboxylate anions undergo highly specific charge remote fragmentations that are entirely consistent with the chemistry of carboxylate anions desorbed from free fatty acids. This permits both identification of the modification and assignment of its location on the acid chain. FAB-desorbed alkyl acetyl glycerophosphocholines (platelet-activating factor) do not produce (M-H)-ions. However, significant high mass ions are formed, and these can be collisionally activated for structural characterization.

Fast atom bombardment and tandem mass spectrometry of phosphatidylserine and phosphatidylcholine.

Fast atom bombardment (FAB) desorption of phosphatidylserine and various phosphatidylcholines produces a limited number of very informative negative ions. Especially significant is the formation of (M-H)- ions for phosphatidylserine, a compound which does not yield informative high mass ions by other ionization methods. Phosphatidylcholines do not yield (M-H)- ions but instead produce three characteristic high mass ions, (M-CH+3)-, [M-HN(CH3)+3]- and [M-HN(CH3)+3-C2H2]-. Both classes of lipids also yield anions attributed to the carboxylate components of these complex lipids. FAB desorption in combination with collisional activation allows for characterization of fragmentation and determination of structural features. Collisional activation of the carboxylate anion fragments from the complex lipids is especially informative. Structural characterization of the fatty acid chain can be achieved as the released saturated carboxylate anions undergo a highly specific 1,4-elimination of H2, which results in the losses of the elements of CH4, C2H6, C3H8 . . . in a fashion entirely consistent with the chemistry of carboxylate anions desorbed from free fatty acids. These CnH2n + 2 losses begin at the alkyl terminus and progress along the entire alkyl chain. Modified fatty acids undergo a similar fragmentation; however, the modification affects the series of CnH2n + 2 losses in a manner which permits determining the type of modification and its location on the fatty acid chain.

The effect of early onset of otitis media on educational achievement.

One hundred and forty-four patients from three different pediatric practices were compared using the Science Research Associates (SRA) tests for academic achievement. First, the patients were divided into those who had had three or more attacks of otitis media and those who had had no attacks of otitis media during the first 18 months of life as recorded by their pediatricians. Matched pairs by sex, birth date, occupation of father, school attended and year of testing were made for comparison purposes. Using the one-tailed t-test, a significant difference in the composite score was found favoring the group with no recorded otitis media in the first 18 months of life. All patients were treated with antibiotics.

The myth of the final hazard assessment.

Hazard assessment is a basic tool used in the evaluation and regulation of chemicals, but in spite of this there are many different interpretations of the scope and function of a hazard assessment. Starting from a discussion of the essential elements and conceptual frames involved, an attempt is made to identify the sources of uncertainty that are inherent in a hazard assessment. Problems identified include unambiguous identification of the chemical source, the routes of exposure, and the possible targets to be considered. Inadequacies in effects data are frequent, but unlike many of the other sources of uncertainty, these are often compensated for by the use of safety factors when setting quantitative limits for human or environmental exposure. The inherent uncertainties in the process make periodic revisions of any hazard assessment process inevitable, as new knowledge on routes of exposure and targets becomes available.

Integrated risk assessment or integrated risk management?

Problems of hazard assessment and risk assessment are at the present time the subjects of considerable discussion in the context of the Organisation for Economic Cooperation and Development (OECD) chemical management programs, within the European Community (EEC) and at national levels. A previous article (J. W. Hart and N. J. Jensen, 1990, Regul. Toxicol. Pharmacol. 11, 123-131) discussed the inherent limitations of the hazard assessment of chemicals. The elements of hazard and risk assessment have been described by Bro-Rasmussen (In Risk Assessment of Chemicals in the Environment, M. L. Richardson, Ed., Chap. 24, pp. 437-450, Royal Society of Chemistry, London, 1988). This article is an attempt to illustrate the different elements in hazard and risk assessments in specific risk management areas and to indicate the limitations in these processes. This analysis indicates that there are different requirements for a risk assessment, which depend on its specific purpose. In particular, problems related to the integration of different approaches--and the stage at which integration is possible--are discussed. While the principle subject of the discussion is risk assessment, many of the elements concerned are also a part of priority setting, and this subject is also discussed briefly.

An automated system for bedside verification of the match between patient identification and blood unit identification.

BACKGROUND: The administration of blood to the wrong patient remains the leading cause of acute hemolytic transfusion reactions and subsequent death. A process control system for blood administration was developed that verifies, at the bedside, the match between barcoded patient identification and blood unit identification. STUDY DESIGN AND METHODS: The system is composed of 1) a portable bedside scanner that reads barcoded patient identification and blood unit identification, 2) a host computer system capable of accepting transfusion data from the bedside scanner, 3) printed documentation of the transfusion episode, and 4) audit trail monitoring of whether all steps in the automated patient and blood unit identification process have been performed. Software design, development, and validation protocols followed industry standards. RESULTS: A pilot study was performed over a 2-month period evaluating the blood administration process using the computerized bedside transfusion identification system prototype for transfusions in 39 oncology patients. CONCLUSION: This system controls the blood administration process and includes bedside verification of the match between patient identification and blood unit identification.

An Aeromonas species implicated in ulcer-disease of the cod (Gadus morhua).

Vibrio anguillarum is the most frequently isolated bacterial species involved in ulcer disease in salt water fish. However, an Aeromonas species was very often incriminated in ulcers and septicaemia in cods (Gadus morhua) in Danish coastal areas. These Aeromonas strains were very uniform in their biochemical activities only differing in growth on Simmons citrate agar, and the mean value for the guanine + cytosine content of DNA was 59 per cent with a standard deviation of 0.4. Primary serological investigations demonstrated a possible identity to O and K antigens. The most characteristic biochemical features of these strains were a gas production from glycerol but not from glucose. They were positive in lysine decarboxylase, did not produce indole, and had a typical fermentation pattern of the glycosides. Negative results were found in H2S production, phosphatase and in the utilization of NH4+ and glucose as the only source of N and C. The evident differences from the species described and subspecies of Aeromonas elucidate the weakness of the existing systems of biotyping. A broader conception of the biochemical spectrum for the individual species of Aeromonas combined with serotyping would seem to be a better system for identification, and also for an epidemiological purpose.

The ulcus-syndrome in cod (Gadus morhua). IV. Transmission experiments with two viruses isolated from cod and Vibrio anguillarum.

Vibrio anguillarum is a serious fish pathogenic bacterium, but it was not found capable of producing the ulcus-syndrome by different inoculation methods in cod. It was possible to transmit the ulcus-syndrome from cod with the papulo-vesicular stage to apparently healthy cod, when they were kept in the same aquarium. Scarification and inoculation with ground papule material lead to development of the ulcus-syndrome. Inoculation of rhabdovirus failed to produce the ulcus-syndrome. Intracardial inoculation of an icosahedral virus suspension could produce the initial papulo-vesicular stage of the ulcus-syndrome in 13 out of 57 inoculated cod (23%). In another experiment 8 out of 36 (22%) inoculated cod developed the ulcus-syndrome and 1 out of 24 (4%) in the control group developed the ulcus-syndrome. In a third experiment 20 inoculated cod failed to develop the ulcus-syndrome. In a number of other cases where the icosahedral virus probably was present in the inoculation material the ulcus-syndrome was also produced, but with a lower frequency. It is indicated, that the isolated icosahedral virus plays a role in the pathogenesis of the ulcus-syndrome in cod, and that Vibrio anguillarum is important for the further progress of the disease.

A fish cell line from gonads of cod (Gadus morhua).

Attempts to establish a cell line from cod fins and gonads were employed by a trypsinising and mincing method. The mincing method allowed growth from gonads of fibroblast like cells, which could be subcultivated continuously at 15-20 degrees C. The cell line is susceptible to virus. The mean number of chromosomes is 64. Two genetically different populations of cells are present in the cell line.

Adenovirus-like particles associated with epidermal hyperplasia in cod (Gadus morhua).

Epidermal hyperplasia in cod is described. The hyperplastic tissue contain few small mucosal glands. Adenovirus-like particle were found in the nucleus of the outermost cells of epidermis.

The ulcus-syndrome in cod (Gadus morhua). V. Prevalence in selected Danish marine recipients and a control site in the period 1976--1979.

The ulcus-syndrome in cod occurred in marine recipients receiving effluents from sugar and cellulose factories. The mean percentages in the years 1976--77 were for Køge, Assens and Nykøbing F. 10.8%, 31.5%, and 7.4%, respectively, while two among 4,211 were affected at the control site, Hundested (Fig. 2). The disease was most prevalent in autumn (Fig. 3) and the primary stages 1 and 2 with papules and erosions were dominating (Fig. 4). One to two year old cod were most frequently attacked by the diseases, but without any significant decrease in condition factor. On the contrary fish with traumatic injuries had a significant lower condition factor than controls (Table II and III). During autumn's 1976-79, 19,238 cod were examined. The mean values for the prevalence of the ulcus-syndrome in Køge, Assens and Nykøbing F. were 12.5%, 41%, and 8%, respectively, while the variations were from 4-20%, 20-48%, and 0-17%, respectively. The problem was negligible at the control site (Table IV). The discussion concerns some aspects that might be of importance for evaluating this pathobiological parameter for use in biological effects monitoring.

Mutagenic investigation of flavourings: dimethyl succinate, ethyl pyruvate and aconitic acid are negative in the Salmonella/mammalian-microsome test.

Three flavourings: dimethyl succinate, ethyl pyruvate and aconitic acid, commonly used in candy, beverages, and baked goods, were tested in the Salmonella/mammalian-microsome test. Tester strains were TA 1535, TA 100, TA 1537 and TA 98 and doses were 32, 160, 800, 4000 and 20 000 micrograms per plate. All tests were performed with and without the S9 fraction from Aroclor induced rat liver. None of the flavourings showed mutagenic potential. These results support the classification made by the Council of Europe, List I (1981).